Ornithine transcarbamylase deficiency

Ornithine transcarbamylase deficiency, often called OTC deficiency, is the most common urea cycle disorder in humans. The defective enzyme, ornithine transcarbamylase, performs the last step in the first part of the urea cycle by turning carbamoyl phosphate and ornithine into citrulline. The disorder is inherited in an X-linked recessive manner, so males are affected more often than females. In severely affected people ammonia levels rise quickly and can cause ataxia, lethargy and death unless treated rapidly. Diagnosis combines clinical findings with biochemical testing and is usually confirmed by molecular genetic methods. Treatment aims to avoid triggers that raise ammonia, most often a low protein diet with nitrogen scavenging medicines, and liver transplant is regarded as curative. Early gene therapy trials with adenoviral vectors ended after the death of participant Jesse Gelsinger.